Taiping, China
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Wang C.-Y.,98 Hospital of PLA | Yang S.-F.,81 Hospital of PLA | Wang Z.,98 Hospital of PLA | Tan J.-M.,98 Hospital of PLA | And 4 more authors.
Journal of Bone and Mineral Metabolism | Year: 2013

Osteoblasts play a crucial role in bone formation. However, the molecular mechanisms involved in osteoblast differentiation remain largely unclear. Runt-related gene 2 (Runx2) is a master transcriptional factor for osteoblast differentiation. Here we reported that p300/CBP-associated factor (PCAF) directly binds to Runx2 and acetylates Runx2, leading to an increase in its transcriptional activity. Upregulation of PCAF in MC3T3-E1 cells increases the expression of osteogenic marker genes including alkaline phosphatase (ALP), osteocalcin (Ocn), and Osteopontin (Opn), and ALP activity was stimulated as well. Consequently, the mineralization of MC3T3-E1 cells was remarkably improved by PCAF. In contrast, PCAF knockdown decreases the mRNA levels of ALP, Ocn, and Opn. ALP activity and the mineralized area were attenuated under PCAF knockdown conditions. These results indicate that PCAF is an important regulator for promoting osteoblast differentiation via acetylation modification of Runx2. © 2013 The Japanese Society for Bone and Mineral Research and Springer Japan.


Wang M.,411 Hospital of PLA | Deng X.,411 Hospital of PLA | Ying Q.,411 Hospital of PLA | Jin T.,411 Hospital of PLA | And 2 more authors.
Biochemical and Biophysical Research Communications | Year: 2015

MicroRNA-224 is overexpressed in various malignant tumors with poor prognosis, which plays a critical role in biological processes including cell proliferation, apoptosis and several developmental and physiological progressions. However, the potential association between miR-224 and clinical outcome in patients with meningiomas remains unknown. Here, we investigate miR-224 expression and biological functions in meningiomas. MiR-224 expression was measured by Northern blot analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in meningioma and normal brain tissues. Kaplan-Meier analysis and Cox regression analysis were used to exam its correlation with clinicopathological features and prognostic value. The biological effects of miR-224 on the cell proliferation and apoptosis in meningioma cells were examined by MTT assay and apoptosis assay. We found the expression levels of miR-224 were significantly higher in meningioma tissues than that in normal brain, positively correlated with advanced pathological grade. Kaplan-Meier analysis indicated that meningioma patients with low miR-224 expression exhibited significantly prolonged overall and recurrence-free survival. Furthermore, we demonstrated that ERG2 was an identical candidate target gene of MiR-224 in vitro. Our results indicated that downregulation of miR-224 suppressed cell growth and resulted in the enhancement of cell apoptosis through activation of the ERG2-BAK-induced apoptosis pathway. Our findings imply the miR-224 expression could predict the overall survival and recurrence-free survival of patients with meningioma and it might be a promising therapeutic target for treating malignant meningiomas. © 2015 Elsevier Inc.


Chen W.,Shanghai Xujiahui Community Medical Service Center | Wang Q.,81 Hospital of PLA | Liu M.,Nanjing University of Traditional Chinese Medicine | Ding X.-B.,Shanghai Xujiahui Community Medical Service Center
Tumor Biology | Year: 2014

Many studies have examined the association between APE1 Asp148Glu (rs3136820) polymorphism gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. PubMed and CNKI databases were searched for case-control studies published up to October 2013. Data were extracted, and pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated. Ultimately, 14 studies, comprising 4,165 lung cancer cases and 5,438 controls were included. Overall, for Glu carriers (Asp/Glu + Glu/Glu) versus wild-type homozygotes (Asp/Asp), the pooled OR was 1.05 (95 % CI = 0.96-1.15 P = 0.000 for heterogeneity); for Glu/Glu versus Asp/Asp, the pooled OR was 1.07 (95 % CI = 0.95-1.21 P = 0.007 for heterogeneity). In the stratified analysis by ethnicity, the significantly risks were not found among Asians or Caucasians. This updated meta-analysis suggests that the APE1 Asp148Glu polymorphisms are not associated with lung cancer risk among Asians or Caucasians. © 2013 International Society of Oncology and BioMarkers (ISOBM).


Zhan P.,Nanjing Chest Hospital | Wang Q.,81 Hospital of PLA | Qian Q.,Nanjing Chest Hospital | Yu L.-K.,Nanjing Chest Hospital
Translational Cancer Research | Year: 2013

Background: Anorexia-cachexia syndrome (ACS) often occurs in patients with advanced cancer. To evaluate the effect of megestrol acetate (MA) in cancer patients with ACS, a meta-analysis of published randomized controlled trials (RCT) was performed. Methods: The databases of PubMed and Web of Science were searched from January 1966 until April 2013 and abstracts presented at American Society of Clinical Oncology conferences were searched to identify relevant clinical trials. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated. Results: Data from a total of 1,142 cancer patients with ACS in 11 RCTs were identified and included for meta-analysis. Cancer patients with ACS who received MA had increased weight gain (179 events among 534 patients treated with MA vs. 83 events among 447 control patients; RR 2.17; 95% CI: 1.59-2.97), and increased appetite improvement (174 events among 321 patients treated with MA vs. 53 events among 280 control patients; RR 4.68; 95% CI: 3.25-6.76). Conclusions: The use of MA can improve appetite and is associated with weight gain in cancer patients with ACS. Despite the fact that these patients are receiving palliative care they should be informed of the risks involved in taking MA. © 2011-2016 Translational Cancer Research.


Ji Y.-N.,Nanjing University of Traditional Chinese Medicine | Wang Q.,81 Hospital of PLA | Li Y.,Nanjing University of Traditional Chinese Medicine | Wang Z.,Nanjing Southeast University
Tumor Biology | Year: 2014

Vascular endothelial growth factor A (VEGF-A) is considered as a prime mediator of angiogenesis and has been implicated in carcinogenesis and metastasis. Various studies examined the relationship between VEGF-A overexpression with the clinical outcome in patients with gastric cancer, but yielded conflicting results. Electronic databases updated to September 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between VEGF-A overexpression and survival of patients with gastric cancer. Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of 20 studies that evaluated the correlation between VEGF-A overexpression and survival in patients with gastric cancer. Combined hazard ratios suggested that VEGF-A overexpression had an unfavorable impact on overall survival (OS) (hazard ratio [HR] = 1.57; 95 % confidence interval [CI], 1.30-1.84) and disease-free survival (DFS) (HR = 1.85; 95 % CI, 1.39-2.32) in patients with gastric cancer. No significant heterogeneity (P = 0.487) was observed among 16 studies for OS and among 7 studies for DFS (P = 0.435). VEGF-A overexpression indicates a poor prognosis for overall survival and disease-free survival in patients with gastric cancer. © 2013 International Society of Oncology and BioMarkers (ISOBM).


Lin Y.,Nanjing University | Lin Y.,Nanjing Medical University | Wang K.,Nanjing Medical University | Hu C.,Jiangsu Province Institute of Traditional Chinese Medicine | And 3 more authors.
Evidence-based Complementary and Alternative Medicine | Year: 2014

Elemene, a compound found in an herb used in traditional Chinese medicine, has shown promising anticancer effects against a broad spectrum of tumors. In an in vivo experiment, we found that apatinib, a tyrosine kinase inhibitor that selectively inhibits VEGFR2, combined with elemene injection (Ele) for the treatment of H22 solid tumor in mice resulted in worse effectiveness than apatinib alone. Moreover, Ele could protect HepG2 cells from death induced by serum-free starvation. Further data on the mechanism study revealed that Ele induced protective autophagy and prevented human hepatoma cancer cells from undergoing apoptosis. Proapoptosis effect of Ele was enhanced when proautophagy effect was inhibited by hydroxychloroquine. Above all, Ele has the effect of protecting cancer cells from death either in apatinib induced nutrient deficient environment or in serum-free induced starvation. A combination of elemene injection with autophagy inhibitor might thus be a useful therapeutic option for hepatocellular carcinoma. © 2014 Yan Lin et al.


Xu C.-H.,Nanjing Chest Hospital | Wang Q.,81 Hospital of PLA | Zhan P.,Nanjing Chest Hospital | Qian Q.,Nanjing Chest Hospital | Yu L.-K.,Nanjing Chest Hospital
Molecular Biology Reports | Year: 2014

Many studies have examined the association between the GSTP1 Ile105Val (rs 1695) gene polymorphism and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed and CNKI database was searched for case-control studies published up to July 2012. Data were extracted and pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated. Ultimately, 42 studies, comprising 12,304 lung cancer cases and 15,729 controls were included. Overall, for G allele carriers (GA + GG) versus homozygote AA, the pooled OR was 1.05 (95 % CI 0.99-1.10 P = 0.092 for heterogeneity), for GG versus AA the pooled OR was 1.04 (95 % CI 0.96-1.12 P = 0.084 for heterogeneity). In the stratified analysis by ethnicity, gender, histological types of lung cancer and smoking status, a significant association was found in Asians and smokers, not in Caucasian or mixed population, Male, Female population, lung AC, SCC, SCLC or non-smokers. Publication bias was found by using the funnel plot and Egger's test. Overall, there is no evidence showing a significant correlation between GSTP1 Ile105Val gene polymorphism and lung cancer risk in overall population, however stratified analysis by ethnicity, histology, gender and smoking status, it correlate with increased lung cancer susceptibility among Asians and smokers. © 2014 Springer Science+Business Media.


PubMed | Nanjing Medical University, 81 Hospital of PLA and Jiangsu Province Institute of Traditional Chinese Medicine
Type: | Journal: Evidence-based complementary and alternative medicine : eCAM | Year: 2014

Elemene, a compound found in an herb used in traditional Chinese medicine, has shown promising anticancer effects against a broad spectrum of tumors. In an in vivo experiment, we found that apatinib, a tyrosine kinase inhibitor that selectively inhibits VEGFR2, combined with elemene injection (Ele) for the treatment of H22 solid tumor in mice resulted in worse effectiveness than apatinib alone. Moreover, Ele could protect HepG2 cells from death induced by serum-free starvation. Further data on the mechanism study revealed that Ele induced protective autophagy and prevented human hepatoma cancer cells from undergoing apoptosis. Proapoptosis effect of Ele was enhanced when proautophagy effect was inhibited by hydroxychloroquine. Above all, Ele has the effect of protecting cancer cells from death either in apatinib induced nutrient deficient environment or in serum-free induced starvation. A combination of elemene injection with autophagy inhibitor might thus be a useful therapeutic option for hepatocellular carcinoma.


PubMed | CAS Institute of Botany, 81 Hospital of PLA and China Pharmaceutical University
Type: | Journal: European journal of medicinal chemistry | Year: 2016

A single agent that simultaneously inhibits multiple targets may offer greater therapeutic benefits in cancer than single-acting agents through interference with multiple pathways and potential synergistic action. In this work, a series of hybrids bearing N-phenylquinazolin-4-amine and hydroxamic acid moieties were designed and identified as dual VEGFR-2/HDAC inhibitors. Compound 6fd exhibited the most potent inhibitory activity against HDAC with IC50 of 2.2nM and strong inhibitory effect against VEGFR-2 with IC50 of 74nM. It also showed the most potent inhibitory activity against a human breast cancer cell line MCF-7 with IC50 of 0.85M. Docking simulation supported the initial pharmacophoric hypothesis and suggested a common mode of interaction at the active binding sites of VEGFR-2 and HDLP ((Histone Deacetylase-Like Protein), which demonstrates that compound 6fd is a potential agent for cancer therapy deserving further researching.


PubMed | Nanjing Chest Hospital and 81 Hospital of PLA
Type: Journal Article | Journal: Chinese clinical oncology | Year: 2015

In anemic patients receiving myelosuppressive chemotherapy, erythropoiesis-stimulating agents (ESAs) raise hemoglobin levels and reduce transfusion requirements, but ESA-related safety concerns exist. To evaluate the overall risk of venous thromboembolism (VTE) associated with the use of ESAs, a systematic review and meta-analysis of published randomized controlled trials (RCT) was performed.The databases of PubMed and Web of Science were searched from January 1966 until December 2012 and abstracts presented at American Society of Clinical Oncology conferences held between January 2000 and December 2012 were searched to identify relevant clinical trials. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated.Data from a total of 11,632 patients with cancer in 50 RCTs were identified and included for meta-analysis. Among those patients receiving ESAs, the summary incidences of all-grade VTE were 7.62%. Patients with cancer who received ESAs had increased VTE risks (482 events among 6,238 patients treated with ESA vs. 269 events among 5,394 control patients; RR=1.75; 95% CI, 1.49-2.05). The highest risk of VET was found in patients with ovarian and cervical cancer for 2.45 (1.12-5.33).The use of ESAs was significantly associated with an increased risk of developing VTE in cancer patients receiving this drug. The risks of VTE may vary with various tumor types.

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